Open AccessActivation of the ER stress and calcium signaling in angiomyolipoma
Author(s) -
Barbora Novotna,
Martina Takáčová,
Soňa Hudecová,
Lubomira Lencesova,
J Breza,
Anton Mišák,
Lucia Csáderová,
Silvia Pastoreková,
Oľga Križanová,
J Breza
Publication year - 2016
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2016_505
Subject(s) - angiomyolipoma , unfolded protein response , tsc2 , tsc1 , signal transduction , downregulation and upregulation , biology , cancer research , autophagy , mtorc1 , endocrinology , endoplasmic reticulum , microbiology and biotechnology , kidney , pi3k/akt/mtor pathway , apoptosis , biochemistry , gene
Renal angiomyolipomas (AMLs) are uncommon benign tumors that occur sporadically or as a part of tuberous sclerosis complex (TSC). Risk of life threatening hemorrhage is the main clinical concern. Although several evidences suggest that hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is crucial for these tumors, modulation of other metabolic pathways might affect tumor growth and progression. Therefore, we aimed to further characterize angiomyolipoma by TSC1/TSC2 expression, hypoxic status, expression of endoplasmic reticulum (ER) stress markers and calcium transport from the ER through the inositol 1,4,5-trisphosphate (IP3) receptors. Despite our expectations, angiomyolipoma were not hypoxic, as determined by absent expression of the carbonic anhydrase IX, which is a reliable marker of hypoxia. This was in accord with very low expression of TSC1 (that is associated with HIF activation) and a high expression of TSC2. Angiomyolipoma specimens also showed a significant upregulation of an anti-apoptotic marker Bcl2 when compared to healthy kidney tissue supporting the induction of pro-survival signaling. Moreover, angiomyolipoma specimens showed the overexpression of the ER stress markers XBP1, CHOP and ATF4 as well as of the mediators of calcium metabolism, namely the type 1 and 2, but not the type 3 IP3 receptors. These data suggest that the ER stress response, survival and calcium metabolism-related pathways but not hypoxia is an important component of the angiomyolipoma pathogenesis.